[unreadable] [unreadable] Breast cancer is thought to arise frequently from a small population of stem or progenitor cells that are particularly susceptible to carcinogens. Breast stem cells are long-lived, mostly quiescent cells that are capable of repopulating involuted mammary glands in vivo and expanding preferentially in vitro. The contribution of breast stem cells to breast cancer risk is unproven, but these cells are thought to be central to breast carcinogenesis. The objective of this study is to establish the methodology to quantify and characterize stem cells in random periareolar fine needle aspiration (RPFNA) samples of breast tissue from women at high risk for breast cancer through a pilot study correlating stem cell markers with breast cytomorphology and histomorphology (tissue- based measures of breast cancer risk). Our central hypothesis is that increased numbers of breast stem cells confer elevated risk for the development of breast cancer. This work will provide a novel measure of breast cancer risk and a more targeted approach for breast cancer prevention through the following specific aim: Aim 1: Determine the correlation between benign breast disease and the prevalence of breast stem cells. Our working hypothesis is that increased numbers of breast stem cells elevate the risk of breast cancer and this will be associated with increased prevalence of early and intermediate breast disease (hyperplasia with atypia , lobular or ductal carcinoma in situ, known markers of elevated risk). Evaluation of stem cell markers by immunohistochemistry and real time PCR of RPFNA and biopsy samples will be used. This work is novel in the use of RPFNA to evaluate breast stem cell populations and examination of stem cells and benign breast disease. Overall, this work has the potential to improve our understanding of breast stem cells and cancer risk and refine breast cancer prevention through a novel stem cell-targeted approach. [unreadable] [unreadable] [unreadable]